PROJECT SUMMARY Type 2 diabetes mellitus (DM2) causes significant morbidity and mortality. Diet can be a powerful tool for treatment of DM2, but the potential impact of diet has not been fully realized, which may be because usual recommendations include the challenging goals of caloric restriction and weight loss. An isocaloric, moderate carbohydrate, high protein diet (the Low Biologically Available Glucose, or LoBAG, diet) has been designed specifically for people with DM2, and is unique because it does not require caloric restriction or weight loss to produce beneficial effects. Data from preliminary efficacy studies are exciting, but are limited in generalizability. The purpose of the proposed project is to expand generalizability by testing the effectiveness of the LoBAG diet in people with DM2 who are free-living (given diet instruction and asked to prepare their own food). This project is proposed as a key component of a five-year career development plan for Dr. Anne Bantle, an endocrinologist and early career investigator at the University of Minnesota. Dr. Bantle?s long-term goal is to become an independent clinician investigator with expertise in treatment of DM2, with particular focus on diet and the gut microbiome. Her career development plan will allow her to 1) develop expertise in clinical research as a principal investigator, 2) develop expertise in DM2, diet, and gut microbiome, 3) develop skills necessary to lead an interdisciplinary research team, and 4) generate preliminary data to support future funding applications. Specific career development activities will include completion of a Master?s Degree in Clinical Research, hands- on training through implementation of the proposed research study and as a co-investigator in multicenter clinical trials, instruction in gut microbiome analysis, attendance and participation in research meetings, and ultimately, successful application for independent funding. The proposed research project will test the hypothesis that the LoBAG diet is effective in free-living participants with DM2, and specifically that consumption of the LoBAG diet will result in greater reduction of hemoglobin A1c than consumption of a control diet, without requiring caloric restriction or weight loss. Thirty-eight participants will be enrolled in a randomized controlled clinical trial of the LoBAG diet versus a control diet over a 12-week intervention period. Specific aims are to 1) determine the effect of the LoBAG diet compared to control on glycemic control, 2) determine the effect of the LoBAG diet compared to control on compliance and quality of life, and 3) determine if features of the gut microbiome are predictive of glycemic response to diet. It is anticipated that this project will generate preliminary data for a future larger, definitive effectiveness trial. The skills and expertise gained from the proposed career development plan and research project will allow Dr. Bantle to successfully emerge as an independent investigator, and will lay the groundwork for her to become a leading scientist in the field of DM2, diet, and gut microbiome.